In an organism such as a mammal, the skin or the mucosa is at the interface with the external environment. The organism is in contact with pathogenic microorganisms, parasites, or many substances such as pathogenic antigens and food antigens at the interface with the external environment, and is exposed to the risk of the entry of harmful foreign materials into the organism by the contact. To prevent the entry of the foreign materials into the organism, the organism has the immune system, which protects the organism through the action of immunoglobulins.
Immunoglobulin A (IgA) is a type of immunoglobulin present in a mammal and is made up of 2 heavy chains (a chains) and 2 light chains (κ and λ chains). The IgA molecule has 2 antigen-binding sites; however, it forms a dimer by binding via a polypeptide called J chain and has antigen-binding sites in exocrine secretions in the respiratory tract, the intestinal tract, and the like. The dimeric IgA (secretory IgA) plays the leading role in mucosal immunity and functions as the front line of the immune mechanism in the alimentary tract and the respiratory apparatus. Secretory IgA is contained in the colostrum and operative to protect the alimentary tract of a newborn infant from bacterial/viral infection (fetomaternal immunity). The production quantity of IgA in humans is the second largest after IgG among various immunoglobulins. The molecular weight of the monomer is 160,000.
IgA is produced and secreted in the form of a dimer by IgA-producing plasma cells present in the lamina propria of an effector tissue. Thereafter, it is bound to a secreted component expressed on the basal membrane side of mucosal epithelial cells, incorporated into the epithelial cells, and secreted into the lumen side. The secreted component has a role in protecting IgA from degradation by proteinase, and the secretory IgA also has a function as a natural antibody against a dietary protein, a blood group substance, an normal inhabitant, or the like in addition to exhibiting antibody activities against various pathogenic viruses and bacteria. In other words, IgA prevents the entry of microorganisms into the mucosal surface via these systems to play an important role in the biological defense mechanism. Secretory IgA is highly resistant to degradation by enzymes, is not degraded even in the intestinal tract, and is also detected in feces.
In summary, IgA is useful in the prevention of the entry of pathogenic microorganisms or allergen substances from the small intestine, the nose, the bronchial mucosa, or the like and in the maintenance of homeostasis. Particularly, IgA present in the intestinal tract is known to contribute to protection against infection, prevention from the occurrence of allergy by foreign protein, or the like. In artificially fed infants fed on nursery dry milk containing no secretory IgA and patients with IgA deficiency, it is known that IgG against dietary antigen appears with high frequency and the degree of progress of the occurrence of allergic diseases or autoimmune diseases is high. Thus, increased IgA production is expected to contribute to protection against infection, prevention from the occurrence of allergy, or the like.
Various substances have conventionally been disclosed as those capable of promoting the in vivo production of IgA. Disclosed IgA production promoters using peptides as effective ingredients include, for example, an IgA production promoter consisting of a peptide selected from the group consisting of a peptide mixture obtained by hydrolysis of a lactoferrin, a peptide isolated from the peptide mixture, a chemically synthesized peptide, a pharmaceutically acceptable salt thereof, and a mixture thereof (Japanese unexamined Patent Application Publication No. 06-32743) and an IgA production promoter using a milk-derived milk fat globule membrane or a milk K-casein-derived glycomacropeptide as an effective ingredient (Japanese unexamined Patent Application Publication No. 05-339161).
Disclosed IgA production promoters using bacterial cells as an effective ingredient include, for example, an IgA production promoter using cells of Bifidobacterium breve or particular Bifidobacterium cells obtained from the search of cells having the ability to induce antibody as an effective ingredient (Japanese unexamined Patent Application Publication No. 01-242532 or 02-280059), an IgA production promoter using a protoplast or cytoplasmic membrane fraction of a bacterium belonging to the genus Bifidobacterium as an effective ingredient (Japanese unexamined Patent Application Publication No. 04-342533), and an IgA production promoter using a bacterial cell autolysate obtained by keeping a suspension of live cells of a bacterium belonging to the genus Bifidobacterium warm at 40 to 55° C. and pH 6 to 12 for 1 hour or more, as an effective ingredient (Japanese unexamined Patent Application Publication No. 06-234647). In addition, there are also disclosed an IgA production promoter using cells, killed cells, or cells lysed or crushed with chemical/enzymatic treatment or physical treatment, of a bacterium belonging to the genus Enterococcus, as an effective ingredient (Japanese unexamined Patent Application Publication No. 11-92389), and an IgA production promoter using a plant-derived lactic acid bacterium belonging to the genus Lactobacillus such as Lactobacillus delbrueckii, Lactobacillus brevis, Lactobacillus sakei, or Lactobacillus curyatus or a plant-derived lactic acid bacterium belonging to the genus Pediococcus such as Pediococcus pentosaceus, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2007-308419). An IgA production promoter is also disclosed using phycocyanin protein pigment obtained by extraction and purification from a cyanobacterium such as spirulina, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2004-256478).
Disclosed IgA production promoters using components derived from mushrooms as effective ingredients include, for example, an IgA production promoter using a Lentinus edodes mycelium extract as an effective ingredient (Japanese unexamined Patent Application Publication No. 2003-155249), an IgA production promoter using a fruit body of Sparassis crispa and/or a processed product thereof or a mycelium of Sparassis crispa and/or a processed product thereof as an effective ingredient (Japanese unexamined Patent Application Publication No. 2005-97133), and an IgA production promoter using an acidic sugar and an acidic peptide having average molecular weights of 5,000 to 10,000 (inclusive) extracted from a fruit body of Eumycota Thelephoraceae such as Boletopsis leucomelas, Shishitake, or Sarcodon aspratus, as effective ingredients (Japanese unexamined Patent Application Publication No. 2005-75740).
Disclosed IgA production promoters using plant-derived components as effective ingredients include, for example, an IgA production-leveling agent using a component consisting of a citrus fruit or its processed material, particularly preferably a compressed material or fruit rind of an Onsyu mandarin orange, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2005-255574), an immunoglobulin (such as IgA) production promoter using aurapten obtained by use of the fruit rind of a citrus fruit as a raw material and extraction from the raw material of the citrus fruit using a solvent such as ethanol, methanol, hexane, ethyl acetate, or dimethyl sulfoxide (DMSO) and β-cryptoxanthin obtained by use of the pulp or the like of a citrus fruit as a raw material and extraction from the raw material of the citrus fruit using a solvent such as ethanol, methanol, hexane, or ethyl acetate, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2011-116735), and an IgA production promoter using a component extracted from a plant such as Anthriscus cerefolium, Calendula officinalis, Sambucus nigra, or Althaea officinalis, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2011-184300).
Disclosed IgA production promoters using sugar-related components as effective ingredients include, for example, a mucosa immunopotentiating composition enhancing the production of IgA and the like, using a fructo-oligosaccharide as an effective ingredient (Japanese unexamined Patent Application Publication No. 2003-201239), an immunoadjuvant using a phosphorylated saccharide in which a plurality of phosphate groups are bound per one glucan molecule such as cellulose, amylose, glycogen, starch, or dextrin, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2004-43326 or 2005-82494), a secretory IgA production inducer using a cyclic inulooligosaccharide cyclofructan obtained by treating inulin, the main ingredient of a carbohydrate obtained from a root of Jerusalem artichoke, Cichorium intybus, or the like, with a cyclic inulooligosaccharide-producing enzyme, cycloinulooligosaccharide fructanotransferase, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2005-179195), and an antibody production inducer for inducing the production of antibodies such as IgA, using a tea polysaccharide having a molecular weight of 10,000 or more, extracted from tea with water or hot water and containing galacturonic acid, galactose, and arabinose as constituent sugars, as an effective ingredient (Japanese unexamined Patent Application Publication No. 2005-239571).
As described above, various substances are disclosed as those promoting the production of IgA in vivo. However, it has not ever been known that a modified starch such as hydroxypropyl starch has the effect of promoting the production of IgA.